Doctoral Dissertation Research: Epigenetic age estimation in human bone

估计死亡年龄是生物考古和法医研究的核心，用于重建过去的人口统计数据，并从身份不明的遗骸中缩小个人的身份。遗传学的最新进展导致了DNA甲基化标记的识别，这些标记随着年龄的变化而变化，可以用于年龄预测的新方法，但通常使用的组织类型在考古和法医环境中并不总是可用的。在这个博士论文项目中，将对已知年龄范围内的人类骨骼样本进行分析，以确定基因组中随年龄变化最可靠的区域。这些数据将用于开发一种通过骨骼预测个人年龄的方法，与其他组织类型相比，骨骼可能显示出不同的甲基化模式。该项目使用的协议和算法将在网上免费提供，该项目将支持STEM学科的研究生和本科生培训和研究。虽然年龄相关的DNA甲基化变化在表观遗传学领域是众所周知的，但迄今为止进行的大多数研究都是在血液和唾液组织中进行的，这些组织可以很容易地从活着的个体中获得。众所周知，DNA甲基化模式在不同组织类型之间存在显著差异，为特定组织类型开发的表观遗传年龄预测模型不能自动应用于另一种组织类型。因此，为了将基于DNA甲基化的年龄预测扩展到法医环境，有必要对特定的法医相关组织进行更多的研究。在这个项目中，研究人员将首先从通过遗体捐赠计划收集的人骨中生成全基因组DNA甲基化数据集。将从这些骨骼样本中提取DNA，并使用商用阵列在基因组中超过85万个位点测量其DNA甲基化水平。该数据集将进行统计分析，以确定基因组的特定区域，这些区域随着年龄的增长以一种强烈的、可预测的方式变化。这些区域的DNA甲基化模式将用于开发一个可以准确估计实际年龄的统计模型。最后，将制定一项协议，仅在这些与年龄高度相关的基因组区域靶向和测量甲基化水平，这将使年龄估计方法以更低的成本应用。这项资助由美国国家科学基金会和国家司法研究所、调查和法医学办公室联合支持。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Age-at-death estimation is central to bioarchaeological and forensic research, for reconstructing past population demographics and for narrowing down the identity of individuals from their unidentified remains. Recent advances in genetics have led to the identification of DNA methylation markers that change with age and could be used in new methods of age prediction, but generally using tissue types that are not always available in archaeological and forensic contexts. In this doctoral dissertation project, samples of human bone across a range of known ages will be analyzed to determine regions of the genome that change most reliably with age. These data will be used to develop a method of predicting an individual's age from their bones, which may show different patterns of methylation compared with other tissue types. The protocol and algorithms used in this project will be made freely available online, and the project will support graduate and undergraduate training and research in a STEM discipline.While age-associated changes in DNA methylation are well known in the field of epigenetics, most research conducted so far has been in blood and saliva tissues that can be easily obtained from living individuals. DNA methylation patterns are known to differ significantly between tissue types, and epigenetic age prediction models developed for a particular tissue type cannot be automatically applied to another. Therefore, in order to extend the applicability of DNA methylation-based age prediction to forensic contexts, more research on specific forensically relevant tissues is necessary. In this project, the researchers will first generate a genome-wide DNA methylation dataset from human bone collected through a body donation program. DNA will be extracted from these bone samples and their DNA methylation levels will be measured at over 850,000 sites across the genome using a commercially available array. This dataset will be analyzed statistically to identify specific regions of the genome that vary in a strong, predictable manner with age. The DNA methylation patterns at these regions will be used to develop a statistical model that can accurately estimate chronological age. Finally, a protocol to target and measure methylation levels at only these highly age-associated genomic regions will be developed, which will allow the age estimation method to be applied at a much lower costThis grant is jointly supported by NSF and the National Institute of Justice, Office of Investigative and Forensic Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.